Cognitive impairment is common in multiple sclerosis (MS) and adds significantly to the burden of the disease. The ability to predict future cognitive impairment from imaging obtained at disease onset has not been investigated.
62 patients imaged within 3 months of a clinically isolated syndrome were assessed neuropsychologically 7 years later. Baseline and periodic MRI measures of lesions, atrophy and normal-appearing white and grey matter were regressed against neuropsychological scores to explore the best predictors of cognitive outcome.
28 patients had developed clinically definite MS at follow-up and a further nine met revised McDonald criteria for MS. Deficits in speed of information processing and executive function were the most common abnormalities. Poor performance correlated with high anxiety ratings. Baseline T(1) lesion metrics predicted executive deficits, and new T(2) lesions at the 3-month follow-up predicted slowed information processing. An increase in myo-inositol concentration in normal-appearing white matter over the first 3 years was associated with poor executive function.
MRI variables obtained at the onset of a clinically isolated syndrome can predict future development of cognitive abnormalities. Our findings may have implications in monitoring and treating patients.
"Feinstein et al. , Summer et al. , and Audoin et al.  found reduced information processing speed in CIS. Nilsson et al.  and Summers et al.  found changes in executive function and processing speed performance. Glanz et al.  found impairment in working memory, processing speed, and verbal memory. "
[Show abstract][Hide abstract] ABSTRACT: Objective:
To investigate cognitive impairment, to assess optical nerve axonal loss, and to determinate whether there is correlation between optical nerve axonal loss and cognition impairment in Clinically Isolated Syndrome (CIS).
Fifteen CIS patients and 15 controls were submitted to Wechsler memory scale, Rey Auditory Verbal Learning, Rey Complex Figure, Paced Auditory Serial Addition, Digit Span, verbal fluency, stroop color, D2, and Digit Symbol tests. CIS patients were evaluated by optical coherence tomography (OCT) (23 eyes).
CIS patients had worse performance in Paced Auditory Serial Addition Test (PASAT) 2 seconds (P=0.009) and fluency tests (P=0.0038). Optical nerve axonal loss was found more frequently in eyes with previous optic neuritis (ON) (85.7%) than in those without previous ON (21.7%) (P=0.0146). There were no significant correlations between optical nerve axonal loss and cognitive findings.
CIS patients had worse cognitive performance than controls. OCT can detect axonal loss resulting from optical neuritis and subclinical axonal loss in eyes without previous optical neuritis. Optical nerve axonal loss was not correlated with cognition.
"In patients with either RRMS or SPMS, the increase in T1 lesion volume (LV) over time correlates significantly with progressive cerebral atrophy and the change in EDSS score (Sailer et al., 2001; Truyen et al., 1996). Moreover, in patients with CIS, baseline T1 hypointense lesion number and volume are strong predictors of the severity of executive dysfunction (Summers et al., 2008). "
"Treatment with the 44 µg dose of IFN β-1a was associated with better cognitive outcomes, whereas higher T2 lesion load predicted cognitive decline. An association between T2 lesions and cognitive impairment has been reported previously [16,25-28]. As we saw a clear, dose-related effect of treatment on MRI measures and an association between T2 lesions and cognition, it is interesting to speculate on how the effect on different MRI lesion types may translate into cognitive benefits. "
[Show abstract][Hide abstract] ABSTRACT: Conventional magnetic resonance imaging (MRI) has improved the diagnosis and monitoring of multiple sclerosis (MS). In clinical trials, MRI has been found to detect treatment effects with greater sensitivity than clinical measures; however, clinical and MRI outcomes tend to correlate poorly.
In this observational study, patients (n = 550; 18-50 years; relapsing-remitting MS [Expanded Disability Status Scale score ≤4.0]) receiving interferon (IFN) β-1a therapy (44 or 22 µg subcutaneously [sc] three times weekly [tiw]) underwent standardized MRI, neuropsychological and quality-of-life (QoL) assessments over 3 years. In this post hoc analysis, MRI outcomes and correlations between MRI parameters and clinical and functional outcomes were analysed.
MRI data over 3 years were available for 164 patients. T2 lesion and T1 gadolinium-enhancing (Gd+) lesion volumes, but not black hole (BH) volumes, decreased significantly from baseline to Year 3 (P < 0.0001). Percentage decreases (baseline to Year 3) were greater with the 44 μg dose than with the 22 μg dose for T2 lesion volume (-10.2% vs -4.5%, P = 0.025) and T1 BH volumes (-7.8% vs +10.3%, P = 0.002). A decrease in T2 lesion volume over 3 years predicted stable QoL over the same time period. Treatment with IFN β-1a, 44 μg sc tiw, predicted an absence of cognitive impairment at Year 3.
Subcutaneous IFN β-1a significantly decreased MRI measures of disease, with a significant benefit shown for the 44 µg over the 22 µg dose; higher-dose treatment also predicted better cognitive outcomes over 3 years.
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